Dr. Mandana Khalili is an Associate Professor of Medicine at the University of California, San Francisco (UCSF). Her long-term career objectives are to mentor early clinical investigators committed to patient-oriented research and to become a leader in efforts to improve our understanding of the pathogenesis of glucose intolerance in viral hepatitis. Her objectives during this award are to expand her research and mentoring program in multidisciplinary clinical and translational research in viral hepatitis, thereby increasing the pool of new investigators who ultimately become successful independent investigators. Dr. Khalili is an established investigator with significant mentoring experience who is committed to patient- oriented research, as evidenced by her ability to conduct high-quality research and her research leadership roles. Her multidisciplinary clinical and translational research program supported by ongoing extramural funding will serve as the platform for providing mentorship for junior investigators. She will capitalize on the rich academic environment of UCSF and its clinical research training resources, including K30 and K12 career development programs and the Clinical and Translational Sciences Institute to train her mentees to enable them to compete successfully for mentored career development awards in patient-oriented research and their transition to independence as clinical investigators. The pathophysiology, treatment, and prevention of both hepatitis C infection - the most common cause of liver disease in United States - and diabetes have been identified by the National Institutes of Health as high- priority areas of health research. Dr. Khalili's research goals are t continue to conduct clinical investigation in viral hepatitis and its complications that will provie insight into the relationship between hepatitis C and insulin action as well as host and viral interactions in disease pathogenesis. This research plan will provide mentoring and research training opportunities for new and junior clinical investigators in predictive modeling, in complex disease interactions, and in performing state-of-the-art physiologic measurements of insulin resistance and insulin secretion. In addition, the resources from her ongoing research activities will support mentees in performing patient-oriented research in viral hepatitis. The protected time afforded by this award will allow her to maintain her productivity and to achieve her mentorship and research goals.